Prevention of relapse to methamphetamine self-administration by environmental enrichment: involvement of glucocorticoid receptors.


Journal

Psychopharmacology
ISSN: 1432-2072
Titre abrégé: Psychopharmacology (Berl)
Pays: Germany
ID NLM: 7608025

Informations de publication

Date de publication:
Apr 2022
Historique:
received: 29 10 2020
accepted: 21 01 2021
pubmed: 27 3 2021
medline: 9 4 2022
entrez: 26 3 2021
Statut: ppublish

Résumé

In rodents, environmental enrichment (EE) produces both preventive and curative effects on drug addiction, and this effect is believed to depend at least in part on EE's actions on the stress system. This study investigated whether exposure to EE during abstinence reduces methamphetamine seeking after extended self-administration. In addition, we investigated whether these effects are associated with alterations in the levels of glucocorticoid receptors (GR) in the brain and whether administration of GR antagonists blocks methamphetamine relapse. We allowed rats to self-administer methamphetamine for twenty 14-h sessions. After 3 weeks of abstinence either in standard (SE) or EE conditions, we measured methamphetamine seeking in a single 3-h session. Then, we used western blot techniques to measure GR levels in several brain areas. Finally, in an independent group of rats, after methamphetamine self-administration and abstinence in SE, we administered the GR antagonist mifepristone, and we investigated methamphetamine seeking. Exposure to EE reduced methamphetamine seeking and reversed methamphetamine-induced increases in GR levels in the ventral and dorsal hippocampus. In addition, EE decreased GR levels in the amygdala in drug-naive animals, but this effect was prevented by previous exposure to methamphetamine. Administration of mifepristone significantly decreased methamphetamine seeking. The anti-craving effects of EE are paralleled by restoration of methamphetamine-induced dysregulation of GR in the hippocampus. These results provide support for the hypothesis that the effect of EE on methamphetamine relapse is at least in part mediated by EE's action on the brain stress system.

Identifiants

pubmed: 33768375
doi: 10.1007/s00213-021-05770-6
pii: 10.1007/s00213-021-05770-6
doi:

Substances chimiques

Receptors, Glucocorticoid 0
Mifepristone 320T6RNW1F
Methamphetamine 44RAL3456C

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

1009-1018

Informations de copyright

© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

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Auteurs

Céline Nicolas (C)

Université de Poitiers, INSERM, U-1084, Laboratoire des Neurosciences Expérimentales et Cliniques, Poitiers, France.

Rebecca S Hofford (RS)

Department of Psychology, University of Kentucky, Lexington, KY, 40536-0509, USA.

Emilie Dugast (E)

Université de Poitiers, INSERM, U-1084, Laboratoire des Neurosciences Expérimentales et Cliniques, Poitiers, France.
CHU de Poitiers, Poitiers, France.

Virginie Lardeux (V)

Université de Poitiers, INSERM, U-1084, Laboratoire des Neurosciences Expérimentales et Cliniques, Poitiers, France.

Pauline Belujon (P)

Université de Poitiers, INSERM, U-1084, Laboratoire des Neurosciences Expérimentales et Cliniques, Poitiers, France.

Marcello Solinas (M)

Université de Poitiers, INSERM, U-1084, Laboratoire des Neurosciences Expérimentales et Cliniques, Poitiers, France.

Michael T Bardo (MT)

Department of Psychology, University of Kentucky, Lexington, KY, 40536-0509, USA.

Nathalie Thiriet (N)

Université de Poitiers, INSERM, U-1084, Laboratoire des Neurosciences Expérimentales et Cliniques, Poitiers, France. nathalie.thiriet@univ-poitiers.fr.

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